Persistent HIF‐1 Activation by Long‐Term Intermittent Hypoxia

Long‐term (30 days) exposure of rats to intermittent hypoxia (LT‐IH) results in persistent elevation of reactive oxygen species levels in central and peripheral nervous system ( J. Nanduri et al., J. Physiol.2016,2018 ). HIF‐ regulates pro‐oxidant enzyme (POE) genes during IH. Present study examined the effect of LT‐IH on HIF‐1α protein and NADPH oxidase (Nox) 4 mRNA abundances in the carotid body (CB) and adrenal medullae (AM) of LT‐IH treated rats. CB and AM of LT‐IH treated rats exhibited robust increase in HIF‐1α protein, Nox4 mRNA and ROS levels. Remarkably, these effects persisted after recovery in room air for 30d. The effects of LT‐IH on HIF‐1α, Nox 4 mRNA, and ROS abundance were absent in rats treated with digoxin, an inhibitor of HIF‐1α during LT‐IH as well as in mice with partial deficiency of HIF‐1a (HIF‐1α heterozygote mice). These findings suggest that HIF‐1 dependent upregulation of POE genes contributes to LT‐IH induced persistent oxidative stress in the CB and AM. Support or Funding Information Supported by NIH‐ HL‐90554. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .